%T An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype
%L discovery1536203
%P 322-329
%V 82
%J Biological Psychiatry
%A N Direk
%A S Williams
%A JA Smith
%A S Ripke
%A T Air
%A AT Amare
%A N Amin
%A BT Baune
%A DA Bennett
%A DH Blackwood
%A D Boomsma
%A G Breen
%A HN Buttenschøn
%A EM Byrne
%A AD Børglum
%A E Castelao
%A S Cichon
%A TK Clarke
%A MC Cornelis
%A U Dannlowski
%A PL De Jager
%A A Demirkan
%A E Domenici
%A CM van Duijn
%A EC Dunn
%A JG Eriksson
%A T Esko
%A JD Faul
%A L Ferrucci
%A M Fornage
%A E de Geus
%A M Gill
%A SD Gordon
%A HJ Grabe
%A G van Grootheest
%A SP Hamilton
%A CA Hartman
%A AC Heath
%A K Hek
%A A Hofman
%A G Homuth
%A C Horn
%A J Jan Hottenga
%A SL Kardia
%A S Kloiber
%A K Koenen
%A Z Kutalik
%A KH Ladwig
%A J Lahti
%A DF Levinson
%A CM Lewis
%A G Lewis
%A QS Li
%A DJ Llewellyn
%A S Lucae
%A KL Lunetta
%A DJ MacIntyre
%A P Madden
%A NG Martin
%A AM McIntosh
%A A Metspalu
%A Y Milaneschi
%A GW Montgomery
%A O Mors
%A TH Mosley
%A JM Murabito
%A B Müller-Myhsok
%A MM Nöthen
%A DR Nyholt
%A MC O'Donovan
%A BW Penninx
%A ML Pergadia
%A R Perlis
%A JB Potash
%A M Preisig
%A SM Purcell
%A JA Quiroz
%A K Räikkönen
%A JP Rice
%A M Rietschel
%A M Rivera
%A TG Schulze
%A J Shi
%A S Shyn
%A GC Sinnamon
%A JH Smit
%A JW Smoller
%A H Snieder
%A T Tanaka
%A KE Tansey
%A A Teumer
%A R Uher
%A D Umbricht
%A S Van der Auwera
%A EB Ware
%A DR Weir
%A MM Weissman
%A G Willemsen
%A J Yang
%A W Zhao
%A H Tiemeier
%A PF Sullivan
%D 2017
%N 5
%O © Society of Biological Psychiatry, 2016. This manuscript version is made available under a Creative Commons Attribution Non-commercial Non-derivative 4.0 International license (CC BY-NC-ND 4.0). This license allows you to share, copy, distribute and transmit the work for personal and non-commercial use providing author and publisher attribution is clearly stated. Further details about CC BY licenses are available at https://creativecommons.org/licenses/. Access may be initially restricted by the publisher.
%C United States
%X BACKGROUND: The genetics of depression has been explored in genome-wide association studies that focused on either major depressive disorder or depressive symptoms with mostly negative findings. A broad depression phenotype including both phenotypes has not been tested previously using a genome-wide association approach. We aimed to identify genetic polymorphisms significantly associated with a broad phenotype from depressive symptoms to major depressive disorder. METHODS: We analyzed two prior studies of 70,017 participants of European ancestry from general and clinical populations in the discovery stage. We performed a replication meta-analysis of 28,328 participants. Single nucleotide polymorphism (SNP)-based heritability and genetic correlations were calculated using linkage disequilibrium score regression. Discovery and replication analyses were performed using a p-value-based meta-analysis. Lifetime major depressive disorder and depressive symptom scores were used as the outcome measures. RESULTS: The SNP-based heritability of major depressive disorder was 0.21 (SE = 0.02), the SNP-based heritability of depressive symptoms was 0.04 (SE = 0.01), and their genetic correlation was 1.001 (SE = 0.2). We found one genome-wide significant locus related to the broad depression phenotype (rs9825823, chromosome 3: 61,082,153, p = 8.2 × 10(-9)) located in an intron of the FHIT gene. We replicated this SNP in independent samples (p = .02) and the overall meta-analysis of the discovery and replication cohorts (1.0 × 10(-9)). CONCLUSIONS: This large study identified a new locus for depression. Our results support a continuum between depressive symptoms and major depressive disorder. A phenotypically more inclusive approach may help to achieve the large sample sizes needed to detect susceptibility loci for depression.
%K CHARGE consortium, Depressive symptoms, FHIT gene, Genome-wide association study, Major depressive disorder, Psychiatric Genomics Consortium